Variant 6-118314152-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001029858.4(SLC35F1):c.1127C>A(p.Pro376His) variant causes a missense change. The variant allele was found at a frequency of 0.000546 in 1,614,174 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 3 hom. )

Consequence

SLC35F1
NM_001029858.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

Variant links:

Genes affected

SLC35F1 (HGNC:21483): (solute carrier family 35 member F1) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC35F1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030665606).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35F1	NM_001029858.4 linkuse as main transcript	c.1127C>A	p.Pro376His	missense_variant	8/8	ENST00000360388.9	NP_001025029.2
SLC35F1	NM_001415931.1 linkuse as main transcript	c.1127C>A	p.Pro376His	missense_variant	8/9		NP_001402860.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35F1	ENST00000360388.9 linkuse as main transcript	c.1127C>A	p.Pro376His	missense_variant	8/8	1	NM_001029858.4	ENSP00000353557	A2	Q5T1Q4-1
SLC35F1	ENST00000621341.1 linkuse as main transcript	c.950C>A	p.Pro317His	missense_variant	7/7	5		ENSP00000484738	P2	Q5T1Q4-2

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000660

AC:

166

AN:

251484

Hom.:

AF XY:

0.000743

AC XY:

101

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000867

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000853

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000552

AC:

807

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000627

AC XY:

456

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000575

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000492

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000376

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000910

Hom.:

Bravo

AF:

0.000563

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000618

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.00124

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.1127C>A (p.P376H) alteration is located in exon 8 (coding exon 8) of the SLC35F1 gene. This alteration results from a C to A substitution at nucleotide position 1127, causing the proline (P) at amino acid position 376 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.91

P;.

Vest4

0.41

MVP

0.38

MPC

1.4

ClinPred

0.16

GERP RS

5.6

Varity_R

0.23

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over